Local extension of HMGB1 in atherosclerotic lesions of human main cerebral and carotid arteries.

High mobility group box 1 protein (HMGB1) is a non-histone chromosomal protein which is highly conserved, ubiquitous, and widely distributed. HMGB1 has multiple functions in the nucleus, including the maintenance of nucleosome structure, the regulation of gene transcription, and involvement in DNA recombination. HMBG1 is currently recognized to have a wide range of potential functions and pathological relevance. HMGB1 is released into the extracellular space from necrotic cells and from activated macrophages. HMGB1 binds to the receptor for advanced glycation end products, resulting in the induction of inflammatory cytokines, and to endothelial cell thrombomodulin. HMGB1 neutralization may also reduce the development of atherosclerosis and ameliorate brain infarction. We investigated the immunolocalization of HMGB1 in atherosclerotic lesions of human cerebral and carotid arteries using a specific antibody, and confirmed the detailed expression and cell type localization using double immunofluorolabeling. In the main cerebral arteries, this anti-HMGB1 antibody intensely immunolabeled both normal morphological vascular smooth muscle cells (VSMCs) within the tunica media and infiltrating VSMCs within the intima of thickened fibrous cap plaques. Endothelial cells were also positive for HMGB1. In carotid plaques, HMGB1-like immunoreactivity (IR) was intense in macrophages, although this IR decreased with increasing cell size. Medium-sized foam cells (50-150 µm) were the most intensely stained. This IR was also observed in the nuclei of foam cells and VSMCs. These findings may provide a basis for understanding the association of HMGB1 with atherosclerotic lesions of the cerebral and carotid arteries, and for constructing strategies to counteract atherosclerosis with anti-HMGB1 antibody.

Telomere length shortening in patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Shortened telomere length has been considered to be associated with various age-related diseases, especially in dementia such as Alzheimer's disease and vascular dementia. However, changes in telomere length in dementia with Lewy bodies (DLB) remain unclear. To elucidate these changes, we set out to determine telomere length in peripheral leukocytes as well as the level of urinary 8-hydroxy-deoxyguanosine (8-OHdG) as a marker of oxidative stress in DLB. METHODS: Blood samples were obtained from 33 patients with a clinical diagnosis of probable DLB and 35 age-matched, non-demented elderly controls (NEC). Telomere length was assessed by quantitative real-time polymerase chain reaction of genomic DNA extracted from leukocytes, whereas oxidative stress was assessed on the basis of urine 8-OHdG level, which was measured using high-performance liquid chromatography. RESULTS: Telomere length was significantly shorter in the DLB group than in the NEC group. Urinary 8-OHdG levels were significantly higher in the DLB group than in the NEC group. There was a negative correlation between telomere length and age in the DLB group; however, there were no significant relationships between telomere length and clinical findings including disease duration, severity of cognitive decline, presence or absence of fluctuation in cognitive function, visual hallucinations, and Parkinsonism. In both groups, the correlation between telomere length and urinary 8-OHdG levels was not significant. CONCLUSIONS: These findings indicate that the etiopathology of DLB is considered to be an accelerated aging process.

[Present status and problems in medical care for demented patients using public counselling facilities].

To clarify the present status and problems in medical care for the elderly with dementia, 103 cases were studied according to the descriptive records obtained at a public counselling facility for dementia, based on interviews with patients' families. Their records were analysed based on their background, severity of dementia (clinical dementia rating: CDR), and counselling content. There were 75 demented patients with a CDR score of 1 or more, and 50 of them were women aged 54 to 90, while the remaining 25 men were aged 55 to 88. The consultation content was clustered into 5 codes: code 1, evaluation of dementia and/or dementia-related symptoms including psychiatric symptoms and behavioral disturbance; code 2, methods to manage patients; code 3, methods to take a patient to a medical institution; code 4, questions regarding medical treatment and drugs prescribed at present; code 5, information on the welfare resources provided. In most of the 75 patients, the degree of dementia deteriorated insidiously without any physical symptoms. The key person and/or caregiver was usually an elderly spouse, and the family noticed dementia only after cognitive impairment progressed with or without troublesome symptoms. Hallucination was a common troublesome symptom. Concerning consultation content, codes 1, 2, and 3 were common, while 13 cases had dissatisfaction with their medical treatment. Therefore, it was necessary to explain the significance of early diagnosis of dementia to families and their caregivers. There were also many families who felt strain and wondered about what hospital or department to take the patient to. In addition, it seemed that explanation on the clinical course and adverse drug reactions, advice for the correspondence with psychiatric symptoms and abnormal behaviour, and information services concerning utilization of social resources was not yet sufficient.

[Five elderly patients with cerebral infarction seen during a heat wave].

Five elderly patients (> or = 65 y) with cerebral infarction induced by dehydration during a heat wave were described to clarify the relationship between dehydration and stroke in the aged. When the daily maximum temperature exceeded 30 degrees C every day for two weeks, 6 patients with acute stroke came to our hospital. Five of them were patients with cerebral infarction aged 73-89 (the elderly group) and one was a 52-year-old woman with putaminal hemorrhage. As control groups, patients with ischemic stroke during the period 4 weeks before and after, but excluding the heat wave period, which consisted of an elderly control group (n = 7) and a young control group (n = 5), were also studied retrospectively with regard to clinical findings and neuroimaging. The incidence of cerebral infarction in the elderly group was higher in the heat wave period among all three groups. Atherothrombotic, lacunar, and cardioembolic infarctions were seen in 1, 2 and 2 cases, respectively. The onset in the elderly group was characteristic as all occurred before noon and were related to exercise. Physical examination at arrival revealed decreased skin turgor and dry tongue. A high BUN/creatinine ratio (> or = 25) and elevated fibrinogen (> 400 mg/dl) was frequently noted, although high hematocrit (> or = 45) was not seen. According to clinical findings, dehydration was diagnosed and they were infused with fluid, resulting in the improvement of skin turgor and tongue moisture. These findings indicated that dehydration due to excess perspiration due to the heat wave induced cerebral infarction in the elderly. It suggests that water intake on awakening in summer is important to prevent dehydration and ischemic stroke because elderly people are especially susceptible to those conditions in the morning.

Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation.

To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N(epsilon)-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.

[Brain computerized tomographic and ultrasonographic findings in patients with asymptomatic carotid bruits].

This study was conducted to clarify brain and carotid lesions in patients with asymptomatic carotid bruits and their characteristics. We studied 37 patients with carotid bruits, who had various diseases other than stroke and were all neurologically normal, using by brain computerized tomography (CT) and ultrasonography (US). On CT, localized low density areas (LDAs) and their distribution were assessed, as well as the grade of periventricular lucency (PVL). Carotid lesions on US were classified into 3 categories: plaque (locally thickened intima-media complex of 2.1 mm or more in thickness), stenosis (narrowed lumen between 50% and 90% of the linearly measured diameter), and occlusion (severely narrowed lumen more than 90%). Ankle pressure index (API) less than 0.9 was defined as low. Mean age was 73.2 years-old and 28 of them were men. Bruits were heard bilaterally in 15 patients. CT findings showed LDA in 13 patients (35%) and severe PVL in 12 patients (32%). Twenty-three LDAs (13 in the left hemisphere and 10 in the right hemisphere) were seen and all were considered to be infarctions. Nineteen LDAs, 13 of them seen in the basal ganglia, were lacunae. Another 3 LDAs were seen in the watershed zone between the middle and posterior cerebral arteries, whereas the remaining one was a small cortical infarction in the left premotor area in the middle cerebral artery territory. Ultrasonography showed carotid lesions in 65 of 74 carotid arteries (plaque in 28, stenosis in 26, and occlusion in 11) and low API in 18 of 37 patients. Compared with patients with normal CT finding, the frequency of hypertension (92% vs 50%) and ischemic heart disease (69% vs 29%) was significantly high in 13 patients with silent infarction, although there was no difference in US findings. In the hemisphere ipsilateral to the carotid with bruits, which was frequently stenotic, the frequency of infarction was similar to that in the hemisphere ipsilateral to the carotid with no bruit. Regression analysis revealed that hypertension significantly correlated with the presence of cerebral infarction. These findings indicated that incidence of infarction in the elderly patients with asymptomatic carotid bruits was high and was associated with hypertension and advanced atherosclerosis in many organs, including the carotid and peripheral arteries. The reason for the lack of symptoms was considered to be that most of the infarctions were lacunae and located in the basal ganglia, although infarction did not significantly correlate with bruits or carotid lesions.

Presence of Cu/Zn superoxide dismutase (SOD) immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD.

This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.

Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese.

To clarify the role of genetic factors in atherosclerotic plaque formation in the carotid artery and magnetic resonance imaging abnormalities in the brain, we investigated the association of these abnormalities with the angiotensin-converting enzyme (ACE) genotype. One hundred sixty-nine subjects (age, 59.2+/-0.8 years, mean+/-SE) admitted to our hospital for health checkups underwent brain magnetic resonance imaging to evaluate lacunar infarction. B-mode ultrasound examinations of the carotid arteries were performed to detect atherosclerotic plaque. The I/D polymorphism of the ACE gene was determined by the polymerase chain reaction method. Multivariate regression analysis was performed to assess the effects of the following variables on the presence of plaque, mean plaque thickness, and number of plaques: fibrinogen, sex, age, body mass index, mean blood pressure, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, hematocrit, and the D allele of the ACE gene. The frequency of carotid atherosclerotic plaque was significantly (P=.034) higher in subjects with the D allele than in those without this allele. However, the frequency of lacunar stroke was similar in these groups. A multivariate regression analysis showed that the presence of plaque was independently associated with the D allele (odds ratio=3.27, P=.016). However, mean plaque thickness and the number of plaques were not associated with the D allele. The D allele of the ACE gene may be involved in the presence of carotid plaque but not in the extent of this plaque or asymptomatic lacunar stroke in Japanese subjects.

[Deterrent factors in rehabilitation training following cerebral vascular disease--comparison of elderly and non-elderly patients].

The purpose of the present study was to clarify the deterrent factors for rehabilitation training (rehab) of chronic cerebral vascular disease (CVD) patients, and also to evaluate the influence of age on these factors. Sixty-five CVD impatients with sequelae treated at the Cerebral Vascular Center of Nanasawa Hospital were included in the study. Patients were classified into two groups using the Barthel index score: good effect group (n = 21) or no effect group (n = 22). The following factors were compared between the two groups in order to investigate which factor most affects the results of rehab: age, sex, the site of brain damage, extent of motor paralysis, character (Type A character or not), aphasia, hemispacial neglect, depression, and positive attitude toward training. A possible association between depression, and the site of brain damage and Type A character was investigated. Also, the difference in mood disorders was compared between elderly and non-elderly stroke patients. In the elderly group, hemispacial neglect, a negative attitude toward training, and depression all adversely affected the outcome of the rehab. In the non-elderly group, aging, hemispacial neglect, and a negative attitude toward training influenced the effect of the rehab, but there was no correlation with depression. Depression was seen in 64% of the patients (38/59). Of the 38 patients in a depressed state, 24 (63%) had right hemisphere brain damage, 13 (34%) had left hemisphere brain damage, and 1 (3%) had brain stem damage. Twenty-seven of the 38 depressed patients (71%) were Type A character, significantly more than in the non-depressed group (92/21, 43%). In addition, 14 of the 27 Type A patients were aged over 65 years (52%), which was more than in the non-depression group (11/38, 29%).

[An autopsy case of multiple myeloma with pineal body and spinal cord dura mater infiltration].

An autopsy case of multiple myeloma (IgD lambda type) with pineal body and spinal cord dura mater infiltration is reported. The 63-year-old man was diagnosed as multiple myeloma (IgD lambda type). He was treated with melphalan and prednisolone. Extra bone marrow masses developed 1 year after the onset. He died with renal failure. At autopsy there were many extra bone marrow masses including pineal body and dura mater of the thoracic cord. Microscopic examination revealed that those mass lesions consisted of neoplastic plasma cells. Myeloma cells also infiltrated perivascular space near the pineal body, subdural space of the cerebrum and brain stem. The cells were labeled VS 38 c immunohistochemically. We discussed routes of the metastasis to the central nervous system of the multiple myeloma. This case suggests that the way of myeloma cells infiltration to the pineal body is hematogenous metastasis, because pineal body have no blood brain barrier.

[Bladder neck obstruction associated with pontine hemorrhage: report of two cases].

Two male patients presented with urinary retention 6 and 8 months after a stroke. On urodynamic investigation, both had impaired detrusor function and bladder neck obstruction, and 1 had unrelaxing distal urethral sphincter. Abnormalities of ocular movement were present. Magnetic resonance imaging revealed a widespread lesion of the dorsal tegmentum of the pons. Transurethral resection and incision of the prostate enabled them to void without significant residual urine. Pontine hemorrhage may cause neurogenic vesicourethral dysfunction because the pontine micturition center is located in the dorsolateral tegmentum of the rostral pons.

Cerebellar superoxide dismutase expression in Menkes' kinky hair disease: an immunohistochemical investigation.

This comparative immunohistochemical study deals with the expression of the cytosolic Cu/Zn-binding and mitochondrial Mn-dependent superoxide dismutases (SODs) in the cerebella of five patients with Menkes' kinky hair disease (MKHD) and five age-matched controls. Several cell types, including Purkinje cells and reactive astrocytes, of all MKHD patients examined were intensely stained by an antibody to Mn SOD, but not by an anti-Cu/Zn SOD antibody. By contrast, the cells of the five controls reacted very weakly or not at all with the anti-Mn SOD antibody, but were strongly reactive with the antibody to Cu/Zn SOD. These results suggest that the increased Mn SOD immunoreactivity in MKHD reflects enzyme induction as a protective mechanism against the highly toxic superoxide anion generated under the disease conditions.

Cu/Zn superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis.

Cu/Zn superoxide dismutase (SOD)-like immunoreactivity (LI) was found within Lewy body-like inclusions (LBIs) in the spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS) by using an antibody to human Cu/ZnSOD. LBIs were detected in the anterior horn cells in 10 of 20 patients with sporadic ALS. In each of these patients, 7 to 60% of LBIs showed Cu/ZnSOD-LI. No Cu/ZnSOD-LI was detected in intact neurons and glia in the 20 ALS patients, as well as in these cells in 10 normal control individuals. The skein-like inclusions and Bunina bodies, which were found in all of the 20 ALS cases, showed no Cu/ZnSOD-LI. Thus, Cu/ZnSOD appears to play roles in the production and/or degradation process of LBIs.

Demonstration of neurofibrillary tangles and neuropil thread-like structures in spinal cord white matter in parkinsonism-dementia complex on Guam and in Guamanian amyotrophic lateral sclerosis.

This report concerns the demonstration and distribution of neurofibrillary tangles (NFTs), immunoreactive neuropil thread-like structures and dots in the spinal cord gray and white matter of six patients with parkinsonism-dementia complex on Guam and five patients with Guamanian amyotrophic lateral sclerosis (ALS). A monoclonal antibody to Alzheimer NFTs was used. NFTs were found in the spinal cord gray matter and white matter and all patients had immunoreactive neuropil thread-like structures and dots in the gray matter as well as in the white matter. They were particularly numerous in the lateral funiculus of patients with Guamanian ALS.

Comparative immunohistochemical study on the expression of alpha B crystallin, ubiquitin and stress-response protein 27 in ballooned neurons in various disorders.

This report deals with a comparative study on the expression of alpha B crystallin, ubiquitin, stress-response protein 27 (srp 27), srp 72 and phosphorylated neurofilament protein (pNFP) by ballooned neurons in Pick's disease, Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS), leptomeningeal carcinomatosis, anterior spinal artery syndrome and pellagra. Immunohistochemical techniques were used. alpha B Crystallin was expressed by the majority of ballooned neurons of Pick's disease and CJD, but not by those of the other disorders. Ubiquitin and srp 27 expression was also restricted to abnormal neurons of Pick's disease and CJD, but the proportion of stained cells was less than that expressing alpha B-crystallin. There was no evidence of ballooned neurons expressing srp 72. Except for those of pellagra patients, phosphorylated neurofilament protein (pNFP) was detected in most abnormal neurons. Our results suggest that the mechanisms involved in formation and maintenance of swollen neurons in Pick's disease and CJD may be different than those of ballooned neurons in the other entities studied.

Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of alpha B-crystallin, ubiquitin and stress-response protein 27.

This report concerns ultrastructural and immunohistochemical studies on ballooned neurons of ten patients with Creutzfeldt-Jakob disease (CJD). While abundant ballooned neurons and severe white matter degeneration was seen in six Japanese cases, only occasional ballooned neurons and no white matter degeneration was observed in four cases from the files of Montefiore Medical Center. Ultrastructurally, the ballooned neurons contained granule-coated fibrils of 25 to 40 nm in width and 10-nm neurofilaments. The immunohistochemical studies revealed that most ballooned neurons expressed alpha B-crystallin, with deposits of reaction products observed in the cytoplasm. A similar intracellular staining pattern was also seen with the antibody to phosphorylated neurofilament proteins (pNFP). Although the proportion of stained ballooned neurons was less, a positive reaction was also observed with antibodies against ubiquitin, stress-response protein 27 (srp 27) and synaptophysin, but not with an antibody to srp 72. Our findings suggest that expression of pNFP and synaptophysin by ballooned neurons may reflect axonal impairment and that the presence of alpha B-crystallin, srp 27 and ubiquitin may be related to the degenerative processes that neurons undergo in CJD.

Immunohistochemical studies on the new type of astrocytic inclusions identified in a patient with brain malformation.

Immunohistochemical studies were carried out on the new type of cerebral cortical astrocytic inclusions recently discovered in a 20-year-old patient with maldeveloped brain and micropolygyria. The inclusions appeared as eosinophilic structures (hematoxylin and eosin stain) and did not exhibit argyrophilia (modified Bielschowsky method). The inclusions were strongly stained by the antibody against S-100 protein (S 100) and to a lesser extent by the antibody to microtubule-associated protein 1B (MAP 1B). In contrast to Rosenthal fibers, the astrocytic inclusions did not react with antibodies to alpha B-crystallin, glial fibrillary acidic protein and ubiquitin. No positive reactions were obtained with antibodies against heat-shock protein 27 (HSP 27), HSP 72, actin, vimentin, desmin, cytokeratin, myelin basic protein, beta-tubulin, MAP 2, tau protein, paired helical filament, phosphorylated neurofilament protein (NFP), nonphosphorylated NFP, synaptophysin, cathepsin D, alpha 1-antichymotrypsin, alpha 1-antitrypsin and basic fibroblast growth factor. By immunoelectron microscopy, the products of the reaction with the anti-S 100 antibody appeared as heterogeneous granular deposits and with the antibody to MAP 1B they were randomly scattered throughout the astrocytic inclusions. Our results demonstrate that the immunohistochemical profile of the recently described inclusions differs from that of Rosenthal fibers. Whether the novel inclusions are involved in congenital astrocyte dysfunction and cerebral malformation remains to be established.

[P300 latency in patients with respiratory insufficiency due to sequelae of pulmonary tuberculosis].

We studied latent (mild) pulmonary encephalopathy in 14 patients with mild chronic respiratory insufficiency due to the sequelae of pulmonary tuberculosis. All of the patients were between 49 and 62 (mean age: 57.9). None of them had any impairment of daily activities and apparently had a clear consciousness. First, the P300 component evoked by auditory stimuli was examined. Immediately after that, the PO2, PCO2, pH were measured. Then the Hasegawa's dementia scale, the mini-mental state, the "Kanahiroi" test, Zung's depression score, digit span test were also assessed in the 14 patients. P300 components in 7 age-matched normal volunteers were also examined and compared with those in the 14 patients. The mean P300 latency in the patients were significantly prolonged compared with that in the normal volunteers (p less than 0.01). The P300 latency was well correlated with the PCO2, PO2, pH. The results of the "Kanahiroi" test also correlated with these parameters. We suggest that patients with mild respiratory insufficiency due to the sequelae of pulmonary tuberculosis often have latent (mild) pulmonary encephalopathy, and that P300 latency and the "Kanahiroi" test are very useful to detect and evaluate such latent pulmonary encephalopathy.

[A clinical study in elderly patients with Parkinson's disease using MRI and SPECT--Parkinson's disease and the lacunar state].

Parkinson's disease (PD) is often associated with dementia in elderly patients, and sometimes PD coexists with senile dementia of the Alzheimer type (SDAT) or cerebrovascular disease (CVD) in the elderly. However, since there are few previous clinical studies on the coincidence of, or relationship between PD and CVD, the authors evaluated these aspects in 34 elderly patients with PD using MRI and SPECT. All the patients were over 70 years old. The diagnosis of PD was based on the presence of three symptoms (resting tremor, cogwheel rigidity and bradikinesia) which are characteristic of PD, and the effectiveness of L-DOPA therapy. We therefore believe that patients with vascular Parkinsonism were excluded from our study. In 34 cases, 24 (71%) had MRI evidence of CVD (mainly the lacunar state). In the 10 cases who had no CVD, 2 (20%) had severe dementia and the decrease of regional cerebral blood flow (rCBF) in the temporal and parietal lobes bilaterally correlated with the SPECT findings commonly found in SDAT. A comparison of the rCBF and the results of Hasegawa's dementia score (HDS) (verbal intelligence score) was made between the patients with PD associated with CVD and the patients with PD who had no CVD and no SPECT findings which correlated with SDAT. The rCBF in the frontal lobes and the results of the HDS of the former group were significantly lower than those of the latter. As mentioned above, elderly patients with PD often had CVD, leading to dementia.(ABSTRACT TRUNCATED AT 250 WORDS)